1. Field of the Invention
The present invention relates to a method for measuring the concentration of a component contained in a bodily fluid of a living body and a measuring apparatus therefor. More particularly, the present invention relates to a method and an apparatus for taking a bodily fluid from a living body and measuring the refractive index of a component contained in the bodily fluid by the use of, for example, a surface plasmon resonator device so as to measure the concentration of the component contained in the bodily fluid of the living body.
2. Description of the Background Art
A diabetic or the like has conventionally measured a blood sugar value a plurality of times every day by himself or herself. In such measurement, he or she has taken a blood sample from his or her capillary by using a blood taking tool, and then, has measured the blood sugar value by himself or herself by means of a sensor and measuring instrument exclusive for the measurement.
However, the measurement of the blood sugar value by the diabetic by himself or herself has raised many problems such as a pain at the time of taking the blood every time, hardening of a skin through which the blood is taken and a danger of infection. Therefore, the diabetic who measures the blood sugar value every day has had great expectations of an improvement in a blood sugar value measuring method.
The concentration of a component contained in an intercellular fluid in subcutaneous tissue (i.e., a fluid resulting from the filtration of blood through the wall of a capillary) has a good correlation with the concentration of the blood. In view of this, in recent years, the blood has not been measured, but the intercellular fluid in the subcutaneous tissue is exuded to the surface of the skin from under the skin (hereinafter referred to as “a subcutaneous exuding fluid”). The resultant fluid has been used as a sample to be measured. There have been proposed several measuring methods by which the above-described problems can be solved.
As methods for taking the subcutaneous exuding fluid, there have been proposed a method by means of a small-sized syringe needle and a method by using a laser beam.
In the method by means of a small-sized syringe needle, a small-sized syringe needle 1 has been allowed to be shallowly invaded, thereby taking a subcutaneous interstitial fluid, as shown in FIG. 16. A quantity of fluid taken at a time in this method has been about 1 μL. FIGS. 17A and 17B illustrate the case where a plurality of syringe needles 1 have been used.
In the method by using the laser beam, a fine pore has been formed by irradiating the surface of a skin with a laser beam of minute power, and then, a subcutaneous exuding fluid has been taken through the fine pore. With the laser beam of minute power, it has been possible to remarkably alleviate the pain to a living body.
In the meantime, examples of a method for measuring a very small quantity of a sample such as the subcutaneous exuding fluid include an enzyme reagent method and enzyme electrode methods.
The enzyme reagent method is a method for supplying a sample to be measured to a reaction reagent layer in which an enzyme and a color reagent are mixed together and optically measuring a change in color so as to calculate a concentration. A sample of about 3 μL is needed.
The enzyme electrode method is a method for forming a reagent layer containing an enzyme therein directly on a plurality of electrodes made of carbon or noble metal, supplying a sample to be measured on the resultant reagent layer, decomposing a product resulting from an enzyme reaction by means of the electrodes with the application of a potential, and converting a change in decomposition current quantity into a measurement value by using a special-purpose algorithm.
Alternatively, another enzyme electrode method is a method for forming a reagent layer containing an enzyme therein on a reference electrode made of noble metal or the like and an FET gate which is exposed, supplying a sample on the resultant reagent layer, measuring a change in pH resulting from an enzyme reaction as a change in gate potential, and converting the change into a measurement value by using a special-purpose algorithm.
However, the methods for taking the subcutaneous exuding fluid and the methods for measuring a very small quantity of sample in the prior art described above have raised problems as follows:
First, the method for taking the subcutaneous exuding fluid by the use of the small-sized syringe needle causes a pain since the small-sized syringe needle pierces the skin, causes a danger of infection, and takes time for curing the skin. Moreover, the skin of a human being generally has an excellent elasticity, so that the skin dimples when the needle 1 is intended to be shallowly pierced. Therefore, the invasion depth of the needle 1 is varied per piercing, thereby making a taking quantity inconstant. In the case of the great depth, the blood is mixed with the sample, blood cells adversely influence on measurement accuracy.
It has been conceived that the numerous small-sized syringe needles are arranged so as to stabilize the piercing depth and alleviate the pain in the other method by the use of the small-sized syringe needles, as illustrated in FIGS. 17A and 17B. However, there have arisen problems of a danger that the needle is broken in the skin caused by a decrease in strength of the needle and an increase in fabricating cost.
Next, in the method using the laser beam, it is, indeed, possible to alleviate the pain by using the laser beam of low power, but the subcutaneous exuding fluid cannot be naturally exuded from the fine pore formed at the surface of the skin by the use of the laser beam. The subcutaneous exuding fluid must be forcibly exuded, and therefore, the taking quantity is small. Moreover, the power control of the laser beam is difficult from the technical viewpoint, and further, it is difficult to cope with the states of skins different individually. Although the irradiation of the laser beam a plurality of times may be conceived by adding a feedback function to the power control, operability is reduced in this case.
The method for measuring the very small quantity of sample in the prior art has raised problems as follows:
First, in the enzyme reagent method, the entire quantity of sample required for the reaction is needed at the time of the beginning of the measurement. In the case where the subcutaneous exuding fluid is gradually taken, a supplying system need be provided for reserving the subcutaneous exuding fluid once, and then, supplying it to a reaction system. Moreover, it is difficult to decrease the quantity of sample in the sample layer or the optical measuring system from the viewpoint of secureness of a quality. In addition, in the enzyme reagent method, the sample is thrown away after one measurement, and therefore, it cannot be continuously measured.
In contrast, although a necessary quantity of sample is about 3 μL in the enzyme electrode method, the entire quantity of sample required for the reaction is needed at the time of the beginning of the measurement. Consequently, a supplying system need be provided similarly to the enzyme reagent method. In addition, also in the enzyme electrode method, the sample is disposed of, and therefore, it cannot be continuously measured.
Additionally, in the method for measuring a change in pH according to an enzyme reaction as a change in gate potential, the sample is indispensably diluted. An apparatus is large in size caused by dilution or calibration. Therefore, the sample is needed in a quantity of 5 μL for one measurement. Furthermore, a supplying system need be provided for reserving the subcutaneous exuding fluid.